Environmental factors and gene-environment interactions in the aetiology of asthma.

The importance of early life environmental influences on the aetiology of asthma is implied by the observed geographic and temporal variation in the prevalence of the disease among children. 2. There is evidence pointing to the role of exposure to allergen, various aspects of diet and hygiene-related factors in the aetiology of asthma. 3. There is also evidence that heritable factors influence the impact of hygiene-related exposures on the risk of having asthma. Polymorphism within genes coding for the toll-like receptor-lipopolysaccharide (TLR-LPS) signalling pathway may underlie variations in effects of hygiene-related exposures, including specifically endotoxin, on the risk of developing allergic sensitization and allergic disease. 4. At present there is no unifying theory to explain the childhood origins of asthma and, hence, no solid basis for developing preventative interventions. Progress towards this goal requires better understanding of the heterogeneous nature of the disease in early childhood, improved characterization of relevant environmental exposures and long-term follow up of birth cohorts with reliable and valid measures of allergy and asthma outcomes.